Synthetic progestogens belong to different pharmacological classes and are mixed steroids. They display different properties due to their various affinities to the different steroid receptors. In addition, the dosage used can modify their side effects. Normethyltestosterone used at minimal doses, also called progestogen only pill (POP), constitute the standard recommended hormonal contraception for women with vascular and metabolic contraindications to combined pill (COC). However, POP efficacy and gynecological tolerance are limited. We have developed for more than 20 years in France the use of two pregnane derivatives as contraceptive agents in women with contraindication to COC. Chlormadinone acetate and cyproterone acetate have different antigonadotropic potencies but remain neutral on vascular risk. We have analyzed the efficacy, vascular and gynecological tolerances in 187 women with systemic lupus erythematous with or without antiphospholipids. Venous thrombosis and arterial events rates were lower than those reported in the literature. The current experience in women with thrombophilia is similar as reported in a series of 150 patients. In addition, we have also used antigonadotropic progestins in women with hereditary angioedema (HAE) types I, II or III. HAE symptoms can be induced or worsened by COC. We could demonstrate a significant improvement of the symptoms in most women with HAE under antigonadotropic progestins. Gynecological and general tolerances were satisfactory. In conclusion, antigonadotropic progestins could have clinical positive benefits as contraceptive agents in women with contraindication to COC.